The cost of sequencing an entire human genome continues to plummet. Complete Genomics, a Mountain View, California-based biotechnology company last year claimed it would soon be able to sell full human genome sequences for as little as $5000 apiece. That now appears within reach. In tomorrow's Science, the company will report  that it sequenced three human genomes for about $4400 each, at least in the cost of reagents. Such cheap sequencing could vastly accelerate studies designed to pinpoint genes underlying complex diseases.
The rapid fall in sequencing prices may give genomics an equivalent of Moore's Law, which describes how the number of transistors on computer chips doubles every 18 months, steadily driving down the cost of computing power. In 2003, the cost of sequencing a human genome was an estimated $300 million. That was down to $1 million in 2007 and $60,000 last year.
Researchers at Complete Genomics say they owe their success both to speed and low use of reagents. The sequencing technology works by first chopping the genome into single-stranded DNA fragments and combining them with snippets of known synthetic DNA so that they form small circles of about 400 bases. Each DNA circle is copied over and over so that the DNA winds itself into a 200 nanometer ball. These "DNA nanoballs" are then washed over a slide patterned with sticky spots designed to hold a single ball at each spot. The company uses a modified version of a conventional sequencing technology that attaches a series of 10-base-long fluorescently-labeled DNA snippets to the DNA in the balls, which enables them to work out the sequence of the original DNA. Those provide them with billions of DNA sequences, each of which are about 35 bases long. A computer program then looks for overlaps between these sequences to reconstruct the overall genome.
The technique's advantage, company officials claim, is that the nanoballs assemble themselves into an ultra-dense array, thereby holding down reagent costs and speeding the analysis of the fluorescent signals.
Using the new technology, Complete Genomics' chief scientist Radoje Dramanac estimates that the company will soon be able to sequence a complete human genome in about a day. "For the first time this will enable large numbers of patients to be sequenced to get to the bottom of thousands of genetically controlled diseases," says Dramanac, who is also the lead author of the Science paper. In fact, on Monday, company officials announced a collaboration with researchers at the Institute for Systems Biology in Seattle, Washington, to sequence genomes of 100 patients with Huntington's disease, the largest human genome disease association study conducted to date.
Robert Cook-Deegan, a genomics policy expert at Duke University in Durham, North Carolina, says that after hearing so much hype about the Complete Genomics sequencing technologies, he's impressed with the details. But he also notes that the technology has an error rate of about one in every 100,000 bases. The human genome contains roughly 3 billion letters, meaning there could be as many as 30,000 errors. So there's still room in the marketplace for sequencing technologies that are fast, cheap, and even more accurate.